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Pharmacological Management of
Congestive Heart Failure
Companion Reading (Notes):
Pharmacological Treatment of
Heart Failure (Klabunde)
Drugs Acting on the
Cardiovascular System (Cray)
Formative Assessment
Cardiovascular Pharmacology
Review Test
http://www.emedicine.com/emerg/TOPIC108.HTM
Clinical:
e-Medicine article
Congestive Heart Failure and
Pulmonary Edema
Learning Objectives:
1.
2.
3.
4.
5.
Definition of HF
Classification of HF
There are many different ways to
categorize heart failure, including:
1.
2.
3.
4.
5.
3.
4.
cardiac output may develop deep venous thrombi which may produce
pulmonary emboli and elevation of pulmonary arterial pressure
Other causes:
Thyrotoxicosis
Pregnancy
Infection
Anemia
Rheumatic and other
forms of Myocarditis
Physical, dietary, fluid
Environmental and
emotional excesses
Infective Endocarditis
8
Pathophysiology in HF
HF is summarized best
as an imbalance in
Starling forces or an
imbalance in the
degree of end-diastolic
fiber stretch
proportional to the
systolic mechanical
work expended in an
ensuing contraction.
Pathophysiology in HF(2)
Compensatory Mechanisms During Heart Failure
Cardiac
Frank-Starling mechanism
Ventricular dilation or hypertrophy
Tachycardia
Autonomic Nerves
Increased sympathetic adrenergic activity
Reduced vagal activity to heart
Hormones
Renin-angiotensin-aldosterone system (RAAS)
Vasopressin (antidiuretic hormone/ADH)
Circulating catecholamines
Natriuretic peptides
10
Pathophysiology in HF (2)
From: http://www.pharmacology2000.com/Cardio/HF/HFobj1.htm
11
Source: http://cvphysiology.com/BloodPressure/BP015.htm
12
Source: http://www.mc.uky.edu/pharmacology/instruction/pha824hf/PHA824hf.html
14
15
atrium)
Hepatojugular reflux
Weight loss >4.5 kg in 5 days in response to treatment
17
http://www.fpnotebook.com/CV/Exam/FrmnghmHrtFlrDgnstcCrtr.htm
19
Symptoms
II
III
IV
20
(Clickable)
D= Vasodilator Effect
E= Inotropic Effect
21
24
Overview of HF Pharmacological
Management
Treatment of HF aims
to relieve symptoms,
to maintain a euvolemic state (normal fluid
level in the circulatory system), and
to improve prognosis by delaying
progression of heart failure and reducing
cardiovascular risk
25
Overview of HF Pharmacological
Management(2)
Drugs used include:
Related Terms:
1. contractility (inotropy),
1. diuretic agents,
2. vasodilator agents,
2. heart rate (chronotropy)
3. positive inotropes,
3. conduction velocity
4. ACE inhibitors,
(dromotropy)
5. beta blockers,
6. aldosterone antagonists
26
Overview of HF Pharmacological
Management (3)
Angiotensin-modulating agents
ACE inhibitor (ACE) therapy is recommended
for all patients with systolic heart failure,
irrespective of symptomatic severity or blood
pressure
27
Overview of HF Pharmacological
Management(4)
Angiotensin-modulating agents cont.
ACEIs and ARBs decrease afterload by
antagonizing the vasopressor effect of
angiotensin, thereby decreasing the amount of
work the heart must perform
Overview of HF Pharmacological
Management (5)
Many ACE inhibitors have been developed
30
Overview of HF Pharmacological
Management (6)
Commonly used Angiotensin Converting Enzyme (ACE) Inhibitors
31
Overview of HF Pharmacological
Management(7)
MOA of Angiotensin Converting Enzyme (ACE) Inhibitors
32
Overview of HF Pharmacological
Management (8)
Diuretics
Diuretic therapy is indicated for relief of congestive
symptoms. Several classes are used, with
combinations reserved for severe heart failure
Overview of HF Pharmacological
Management (9)
Diuretics cont.
Potassium-sparing diuretics (e.g.
amiloride) used first-line use to correct
hypokalaemia.
Spironolactone is used as add-on therapy
to ACEI plus loop diuretic in severe HF
Eplerenone (Inspra) is specifically
indicated for post-MI reduction of
cardiovascular risk
34
Overview of HF Pharmacological
Management (10)
Beta blockers
Until recently (within the last 20 years), blockers were contraindicated in HF, owing to
their negative inotropic effect and ability to
produce bradycardia effects which worsen
heart failure
However, current guidelines recommend blocker therapy for patients with systolic heart
failure due to left ventricular systolic dysfunction
after stabilization with diuretic and ACEI therapy,
irrespective of symptomatic severity or blood
pressure
35
Overview of HF Pharmacological
Management (11)
Beta blockers cont.
As with ACEI therapy, the addition of a -blocker can
decrease mortality and improve left ventricular function
Several -blockers are specifically indicated for HF
including:
1. bisoprolol,
2. carvedilol, and
3. extended-release metoprolol
antagonism of 1 inotropic and chronotropic effects decreases
the amount of work the heart must perform
36
Overview of HF Pharmacological
Management (12)
Beta blockers cont.
It is also thought that catecholamines and
other sympathomimetics have an effect
on cardiac remodeling, and blocking their
activity can slow the deterioration of
cardiac function
See: The Importance of Beta Blockers in the Treatment of Heart Failure
American Academy of Family Physicians
37
Overview of HF Pharmacological
Management (13)
CARDIAC GLYCOSIDES (Digitalis )
(Some history)
Cardiac glycosides are one of the oldest
groups of drugs used in cardiovascular
therapeutics
There is evidence of use in Egyptian and
Roman times
William Withering published medical accounts
of use of the "foxglove" for the treatment of
"dropsy."
Originally, extracts of d. purpurea were used
Two active principals, digoxin and digitoxin,
are now used in cardiovascular therapeutics
The uses of these drugs are in heart failure
and supraventricular tachyarrhythmias.
These agents have a low therapeutic index
Digitalis purpurea
(Common Foxglove)
38
Overview of HF Pharmacological
Management (14)
N.B. Cardiac glycosides not first line Tx for HF due to risk of toxicities
Positive inotropes
Digoxin / Cardiac glycosides (a mildly positive inotrope
and negative chronotrope), once used as first-line therapy,
is now reserved for control of ventricular rhythm in
patients with atrial fibrillation; or where adequate control is
not achieved with an ACEI, a beta blocker and a loop
diuretic
There is no evidence that digoxin reduces mortality in HF,
although some studies suggest a decreased rate in hospital
admissions
It is contraindicated in cardiac tamponade and restrictive
cardiomyopathy
39
Overview of HF Pharmacological
Management(15) Cardiac glycosides
Mechanism of Positive
Inotropic Action
http://cvpharmacology.com/cardiostimulatory/digitalis.htm
Overview of HF Pharmacological
Management(15) Cardiac glycosides
Antiarrhythmic Actions
Cardiac glycosides also work in the carotid arch and
baroreceptors to increase the sensitivity of these sites
results
enhanced neural traffic to CNS
cardiovascular centers resulting in enhanced vagal outflow
to the myocardium
At the SA node this increase in vagal tone:
1.
2.
2.
Overview of HF Pharmacological
Management(16) Cardiac glycosides
Pharmacokinetics of Cardiac Glycosides
AGENT
GASTRO
INTESTINAL
ABSORPTION
ONSET
OF
ACTION
(MIN)
PEAK
EFFECT
(HR)
AVERAG
E HALF
LIFE
PRINCIPAL
METABOLIC
ROUTE
(EXCRETORY
PATHWAY)
Digoxin
30 to 100%
15 to 30
1 1/2 to 5
36 to 48
hours
Digitoxin
90 to 100%
25 to 120
4 to 12
4 to 6
days
AVERAGE
DIGITALIZING
DOSES
USUAL
DAILY ORAL
MAINTENAN
CE DOSES
oral
IV
Renal; some
gastrointestinal
excretion
1.25 to
1.5 mg
0.75 to
1.00 mg
0.25 to 0.5 mg
Hepatic; renal
excretion of
metabolites
0.7 to
1.2 mg
1.00 mg
0.1 mg
42
Special Considerations
Factors that can alter the therapeutic response
to cardiac glycosides:
Renal disease decreased renal clearance of digoxin
Drug Interactions that:
a) Decrease bioavailability Cholestyramine
b) Decrease renal clearance Amiodarone ,Verapamil ,
Quinidine
Overview of HF Pharmacological
Management(17)
Positive inotropes cont.
The inotropic agent dobutamine is advised only in the
short-term use of acutely decompensated heart failure,
and has no other uses (Bata1 receptor agonist)
44
Overview of HF Pharmacological
Management (18)
Alternative vasodilators
The combination of isosorbide dinitrate/hydralazine is the
only vasodilator regimen, other than ACE inhibitors or
angiotensin II receptor antagonists, with proven survival
benefits
45
Overview of HF Pharmacological
Management (19)
Exner DV, Dries DL, Domanski MJ, Cohn JN (2001). "Lesser
response to angiotensin-converting-enzyme inhibitor therapy
in black as compared with white patients with left ventricular
dysfunction". N Engl J Med. 344 (18): 13517.
doi:10.1056/NEJM200105033441802.
Taylor AL, etal; (2004). African-American Heart Failure Trial
Investigators. "Combination of isosorbide dinitrate and
hydralazine in blacks with heart failure". N Engl J Med 351
(20): 204957. doi:10.1056/NEJMoa042934.
46
From: Medical Pharmacology at a Glance, 7th Ed. Michael J. Neal. 2012 John Wiley & Sons, Ltd: Pg. 49
47
END OF PRESENTATION
Cardiovascular Physiology
Concepts, 2nd edition,
LLW (2011)